Administration of bicarbonate in patients with metabolic acidosis is an area of medicine that has resulted in some confusion for trainees over the past few decades. In the 1970s, it was really not much of a debatable issue; at that time, it was widely accepted that bicarbonate was a cornerstone of therapy in virtually all patients with metabolic acidosis, including those with lactic acidosis and ketoacidosis, and was a first-line therapy after cardiac arrest. In more recent times, bicarbonate therapy has become more nuanced. As with the approach to correction of hyponatremia (Chapter 7), the approach to correction of metabolic acidosis is very dependent on the clinical context. Type and severity of metabolic acidosis are very important considerations, as are coexisting electrolyte abnormalities.

Hyperchloremic (non-anion gap) acidosis is due to either loss of bicarbonate or gain of nonvolatile acid with resulting titration of bicarbonate. The kidney retains chloride to maintain electroneutrality. Hyperchloremic acidosis should generally be treated with bicarbonate or other alkali, unless the cause is expected to be self-limited. For example, with acute diarrhea or prerenal failure, it may not be necessary to give bicarbonate, as the metabolic acidosis will likely correct on its own once the underlying problem is rectified. However, there should be little disagreement about the importance of treating chronic metabolic acidosis in patients with chronic kidney disease (CKD). In such patients, metabolic acidosis is not expected to improve on its own. Accumulating data indicate that correction of even mild renal acidosis has many beneficial
effects, such as improved nitrogen balance and possibly delayed progression of CKD (de Brito-Ashurst et al., 2009; Mahajan et al., 2010; Phisitkul et al., 2010). Another clear-cut indication for alkali therapy is renal tubular acidosis (RTA), where alkali therapy can prevent permanent complications such as bone disease (Morris and Sebastian, 2002).

A different situation exists with high anion gap acidosis. Most of these disorders are due to overproduction of an organic acid, most commonly lactic acid or ketoacids. For instance, in lactic acidosis, the decrease in serum bicarbonate concentration is directly related to the amount of lactic acid production:

H⁺lactate^–+ HCO₃^– → H2O + CO₂ + Lactate^–

Accumulation of the lactate ion occurs if its rate of production outpaces the rate of urinary excretion plus metabolism. If and when it is metabolized, however, lactate will generate bicarbonate. If lactic acid production diminishes after successful treatment of the underlying disease (e.g., septic shock), the acidosis should correct on its own. Therefore, the role of exogenous bicarbonate therapy in patients with lactic acidosis is controversial (Stacpoole, 1986; Kraut and Madias, 2012). Severe acidemia (pH <7.1) may produce hemodynamic instability because of reduced left ventricular contractility, arterial vasodilation, and impaired responsiveness to catecholamines (Mitchell et al., 1972). However, experimental studies indicate that an increase in systemic pH engendered by bicarbonate therapy can be accompanied by worsening of intracellular acidosis (due to increased production of CO₂ with diffusion of CO₂ into cells). This dissociation between systemic and intracellular pH is most evident in patients with circulatory failure (Weil et al., 1986). Rapid infusion of sodium bicarbonate may increase the Pco₂ (especially in patients with impaired alveolar gas exchange), accelerate the production of lactic acid (due to worsening intracellular acidosis leading to increased anaerobic metabolism), lower the ionized calcium (due to a rapid rise in systemic pH which will increase the number of negative charges on albumin and thus the amount of calcium that is bound to albumin), expand the extracellular space (due to the sodium administered), and raise the serum sodium concentration resulting in hypernatremia (when hypertonic solutions are employed).

There are only a few small randomized studies of bicarbonate therapy in lactic acidosis, and these were done over 20 years ago. In a crossover study, 14 patients with lactic acidosis (serum HCO₃ <17 mEq/L and arterial lactate >2.5 mEq/L) in a single intensive care unit (ICU) received, in random order, 2 mmol/kg of sodium bicarbonate or an equivalent dose of sodium chloride (Cooper et al., 1990). Bicarbonate therapy produced
a significant rise in arterial pH and serum HCO₃, but there were no differences in cardiac output, mean arterial pressure, or pulmonary capillary wedge pressure. In another randomized crossover trial of 10 patients with lactic acidosis comparing sodium bicarbonate (1 mmol/kg) and an equivalent dose of sodium chloride, bicarbonate therapy again significantly increased the arterial pH and serum bicarbonate, but again there was no hemodynamic benefit of bicarbonate (Mathieu et al., 1991).